Investigation of the in Vitro Metabolism of Evodiamine: Characterization of Metabolites and Involved Cytochrome P450 Isoforms

Authors

  • Hong-Zhi Sun,

    Corresponding author
    1. Joint Center for Translational Medicine, Dalian Institute of Chemical Physics Chinese Academy of Sciences and The first Affiliated Hospital of Liaoning Medical University, Dalian, China
    • The First Affiliated Hospital of Liaoning Medical University, Jinzhou, China
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    • These two authors equally contributed to this work.
  • Zhong-Ze Fang,

    1. Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
    2. Liaoning Medical University, Jinzhou, China
    3. Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland
    4. Joint Center for Translational Medicine, Dalian Institute of Chemical Physics Chinese Academy of Sciences and The first Affiliated Hospital of Liaoning Medical University, Dalian, China
    Current affiliation:
    1. Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland
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    • These two authors equally contributed to this work.
  • Yun-Feng Cao,

    1. Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
    2. Joint Center for Translational Medicine, Dalian Institute of Chemical Physics Chinese Academy of Sciences and The first Affiliated Hospital of Liaoning Medical University, Dalian, China
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  • Xiao-Yu Sun,

    1. Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
    2. Joint Center for Translational Medicine, Dalian Institute of Chemical Physics Chinese Academy of Sciences and The first Affiliated Hospital of Liaoning Medical University, Dalian, China
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  • Mo Hong

    1. Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
    2. Joint Center for Translational Medicine, Dalian Institute of Chemical Physics Chinese Academy of Sciences and The first Affiliated Hospital of Liaoning Medical University, Dalian, China
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  • This article was published online on 5 July 2012. It has been drawn to our attention that ‘Evodia rutaecarpa’ is no longer a recognised botanical name. Evodia rutaecarpa (A.Juss.) Benth., Evodia ruticarpa var. bodinieri (Dode) C. C. Huang and Evodia ruticarpa var. officinalis (Dode) C. C. Huang, are cited as the three source species of ‘Fructus Evodiae’ in the Chinese Pharmacopoeia (CP) 2005 edition and there are also many citations in PubMed under the name Evodia. However the genus name should in fact be spelled ‘Euodia’, and as such can be found in The Plant List and the Flora of China, where they are now all synonyms of the accepted name Tetradium ruticarpum (A. Jussieu) T. G. Hartley. The current ed. of the CP (2010) has corrected the genus name to Euodia but has not yet recognised Tetradium. We are pleased to clarify the nomenclature for this plant. This notice is included in the online and print versions to indicate that both have been clarified on 20 September 2012.

Correspondence to: Hong-Zhi Sun, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, 121001, China.

E-mail: cmushz@163.com

Abstract

Evodiamine is the main active alkaloid of Evodia rutaecarpa (E. rutaecarpa) and has been demonstrated to exhibit many pharmacological activities including vasorelaxation, uterotonic action, anoxia and control of body temperature. The present study focused on the metabolism of evodiamine. Human and phenobarbital-induced rat liver microsomal incubation of evodiamine in the presence of NADPH resulted in the formation of five major metabolites (M-1, M-2, M-3, M-4, M-5). Four metabolites (M-1, M-2, M-3 and M-5) were identified to mono-hydroxylated evodiamine and one metabolite (M-4) was identified to be N-demethylated evodiamine. CYP3A4, CYP2C9 and CYP1A2 were identified to be the main CYP isoforms involved in the metabolism of evodiamine in human liver microsomes. Finding new metabolites can help us decipher novel substance basis of efficiency and toxicity. Elucidation of drug metabolizing enzymes will facilitate explaining the individual difference for response to the same drugs or herbs and the potential drug–drug interaction or herb–drug interaction. Taken together, these results are of significance for better understanding the pharmacokinetic behaviour of evodiamine and helpful for clinical application of evodiamine and E. rutaecarpa. Copyright © 2012 John Wiley & Sons, Ltd.

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